Ninety-eight (40%) of 243 acquired immune deficiency syndrome inpatients at Mama Yemo Hospital, Kinshasa, Zaire, presented with a history of diarrhea for at least 1 month. To determine the predictive value of persistent diarrhea for human immune deficiency virus (HIV) infection, 128 consecutive patients presenting at Mama Yemo Hospital with persistent diarrhea were tested for the presence of HIV antibodies. One-hundred seven (84%) of the 128 patients with diarrhea lasting at least 1 month were found to be HIV seropositive. HIV seropositive patients with persistent diarrhea more often had a generalized papular pruritic eruption (p = 0.02), a genital herpes simplex infection (p = 0.05), a history of herpes zoster (p = 0.08), and infection with cryptosporidia (p = 0.006) than HIV seronegative patients with persistent diarrhea. Bacterial enteric pathogens were found in 5 (7%) of the 76 seropositive and in none of the 14 seronegative patients in whom stool cultures were performed. Presently persistent diarrhea in adults in central Africa is strongly associated with HIV infection, but the pathophysiological mechanisms causing this diarrhea remain unclear.